Discovery of Potent, Selective, and Brain-Penetrant Apoptosis Signal-Regulating Kinase 1 (ASK1) Inhibitors that Modulate Brain Inflammation

Animals Brain / drug effects Dose-Response Relationship, Drug Drug Discovery Humans Inflammation / drug therapy MAP Kinase Kinase Kinase 5 / antagonists & inhibitors Mice Mice, Transgenic Molecular Structure Protein Kinase Inhibitors / chemical synthesis Pyrazoles / chemical synthesis Rats Structure-Activity Relationship

Journal

Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531

Informations de publication

Date de publication:
28 10 2021
Historique:
pubmed: 16 10 2021
medline: 15 12 2021
entrez: 15 10 2021
Statut: ppublish

Résumé

Apoptosis signal-regulating kinase 1 (ASK1) is one of the key mediators of the cellular stress response that regulates inflammation and apoptosis. To probe the therapeutic value of modulating this pathway in preclinical models of neurological disease, we further optimized the profile of our previously reported inhibitor

Identifiants

DOI: 10.1021/acs.jmedchem.1c01458 PMID: 34653340
pubmed: 34653340
doi: 10.1021/acs.jmedchem.1c01458
doi:

Substances chimiques

Protein Kinase Inhibitors 0
Pyrazoles 0
pyrazole 3QD5KJZ7ZJ
MAP Kinase Kinase Kinase 5 EC 2.7.11.25
MAP3K5 protein, human EC 2.7.11.25

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

15402-15419

Auteurs

J Howard Jones (JH)

Medicinal Chemistry, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States.

Zhili Xin (Z)

Medicinal Chemistry, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States.

Martin Himmelbauer (M)

Medicinal Chemistry, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States.

Michael Dechantsreiter (M)

Medicinal Chemistry, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States.

Istvan Enyedy (I)

Medicinal Chemistry, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States.

Joseph Hedde (J)

Acute Neurology Research Unit, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States.

Terry Fang (T)

Acute Neurology Research Unit, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States.

Janaky Coomaraswamy (J)

Movement Disorders Research Unit, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States.

Kristopher W King (KW)

Drug Metabolism and Pharmacokinetics, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States.

Paramasivam Murugan (P)

Bioassays, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States.

Joseph C Santoro (JC)

Bioassays, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States.

Thomas Hesson (T)

Bioassays, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States.

Dirk M Walther (DM)

Chemical Biology and Proteomics, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States.

Ru Wei (R)

Chemical Biology and Proteomics, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States.
ORCID: 0000-0002-7646-9046

Fengmei Zheng (F)

Technical Development, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States.

Douglas J Marcotte (DJ)

Physical Biochemistry, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States.

Kerri Spilker (K)

Physical Biochemistry, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States.

P Rajesh Kumar (PR)

Physical Biochemistry, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States.

Ying Liu (Y)

Drug Metabolism and Pharmacokinetics, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States.

Rab Gilfillan (R)

Medicinal Chemistry, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States.

Felix Gonzalez-Lopez de Turiso (F)

Medicinal Chemistry, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States.
ORCID: 0000-0001-9736-0907

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Classifications MeSH

Recherchemedicale.com › Eucaryotes › Animaux › Discovery of Potent, Selective, and...
Recherchemedicale.com › Système nerveux › Système nerveux central › Encéphale › Discovery of Potent, Selective, and...
Recherchemedicale.com › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes toxicologiques › Relation dose-effet des médicaments › Discovery of Potent, Selective, and...
Recherchemedicale.com › Techniques d'investigation › Développement de médicament › Découverte de médicament › Discovery of Potent, Selective, and...
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Discovery of Potent, Selective, and...
Recherchemedicale.com › États, signes et symptômes pathologiques › Processus pathologiques › Inflammation › Discovery of Potent, Selective, and...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › MAP Kinase Kinase Kinases › MAP Kinase Kinase Kinase 5 › Discovery of Potent, Selective, and...
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Discovery of Potent, Selective, and...
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Discovery of Potent, Selective, and...
Recherchemedicale.com › Phénomènes chimiques › Structure moléculaire › Discovery of Potent, Selective, and...
Recherchemedicale.com › Actions chimiques et utilisations › Actions pharmacologiques › Mécanismes moléculaires de l'action pharmacologique › Antienzymes › Inhibiteurs de protéines kinases › Discovery of Potent, Selective, and...
Recherchemedicale.com › Composés hétérocycliques › Composés hétéromonocycliques › Azoles › Pyrazoles › Discovery of Potent, Selective, and...
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Rats › Discovery of Potent, Selective, and...
Recherchemedicale.com › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Relation structure-activité › Discovery of Potent, Selective, and...